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HLA Class I Supertype Classification Based on Structural Similarity

Journal Article · · Journal of Immunology
 [1];  [2];  [3]
  1. University of Tennessee, Knoxville, TN (United States)
  2. Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
  3. University of Tennessee, Knoxville, TN (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
+ Show Author Affiliations
HLA class I proteins, a critical component in adaptive immunity, bind and present intracellular Ags to CD8+ T cells. The extreme polymorphism of HLA genes and associated peptide binding specificities leads to challenges in various endeavors, including neoantigen vaccine development, disease association studies, and HLA typing. Supertype classification, defined by clustering functionally similar HLA alleles, has proven helpful in reducing the complexity of distinguishing alleles. However, determining supertypes via experiments is impractical, and current in silico classification methods exhibit limitations in stability and functional relevance. In this study, by incorporating three-dimensional structures we present a method for classifying HLA class I molecules with improved breadth, accuracy, stability, and flexibility. Critical for these advances is our finding that structural similarity highly correlates with peptide binding specificity. The new classification should be broadly useful in peptide-based vaccine development and HLA–disease association studies.
Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1974324
Journal Information:
Journal of Immunology, Journal Name: Journal of Immunology Journal Issue: 1 Vol. 210; ISSN 0022-1767
Publisher:
The American Association of Immunologists, Inc.Copyright Statement
Country of Publication:
United States
Language:
English

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Cited By (2)

Additional file 1 of HLA-Clus: HLA class I clustering based on 3D structure image January 2023
Additional file 2 of HLA-Clus: HLA class I clustering based on 3D structure dataset January 2023

Figures / Tables (12)

Table I(p. 3)table Table I
Table II(p. 4)table Table II
Table III(p. 4)table Table III
FIGURE 1(p. 5)figure FIGURE 1
FIGURE 2(p. 5)figure FIGURE 2
FIGURE 3(p. 6)figure FIGURE 3
FIGURE 4(p. 7)figure FIGURE 4
FIGURE 5(p. 7)figure FIGURE 5
FIGURE 6(p. 8)figure FIGURE 6
Table IV(p. 9)table Table IV
FIGURE 7(p. 10)figure FIGURE 7
Table V(p. 10)table Table V

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59 BASIC BIOLOGICAL SCIENCES